Feedback control of dimensions in nanopore and nanofluidic devices

ABSTRACT

Nanofluidic passages such as nanochannels and nanopores are closed or opened in a controlled manner through the use of a feedback system. An oxide layer is grown or removed within a passage in the presence of an electrolyte until the passage reaches selected dimensions or is closed. The change in dimensions of the nanofluidic passage is measured during fabrication. The ionic current level through the passage can be used to determine passage dimensions. Fluid flow through an array of fluidic elements can be controlled by selective oxidation of fluidic passages between elements.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.15/242,516 filed Aug. 20, 2016, and entitled FEEDBACK CONTROL OFDIMENSIONS IN NANOPORE AND NANOFLUIDIC DEVICES, which is in turn adivision of U.S. patent application Ser. No. 13/021,544 filed Feb. 4,2011, and entitled FEEDBACK CONTROL OF DIMENSIONS IN NANOPORE ANDNANOFLUIDIC DEVICES, which in turn claims the benefit of U.S.Provisional Patent Application Ser. No. 61/409,353 filed on Nov. 2,2010, and entitled FEEDBACK-CONTROL OF CRITICAL DIMENSIONS IN NANOPOREAND NANOFLUIDIC DEVICES. The complete disclosures of U.S. patentapplication Ser. No. 15/242,516, U.S. patent application Ser. No.13/021,544, and U.S. Provisional Patent Application Ser. No. 61/409,353are all hereby expressly incorporated herein by reference in theirentireties for all purposes.

FIELD OF THE INVENTION

The present invention relates to the microfluidic and nanofluidic arts,and, more particularly, to the fabrication and use of nanoscale fluidicelements and the like.

BACKGROUND OF THE INVENTION

Nanoscale fluidic devices include pores and/or channels formed inselected substrates. A solid-state nanopore may be fabricated throughTEM (transmission electron microscope) drilling through a selectedsubstrate such as silicon nitride. Solid-state nanopores can be used toanalyze biological proteins.

Nanofluidic channels may be fabricated by serial electron beamlithography in order to reach the desired dimensions. Channels can alsobe fabricated using photolithography, nanoimprint lithography andnanotransfer lithography.

SUMMARY OF THE INVENTION

Principles of the invention provide techniques for fabricating fluidicpassages such as nanofluidic channels and nanopores. In one aspect, anexemplary method includes the steps of providing a substrate comprisinga nanofluidic passage bounded by an electrical conductor, filling thenanofluidic passage with an electrolyte, and causing the nanofluidicpassage to at least partially close by electrochemically forming anoxide layer on the conductor. The substrate itself can be comprised ofan electrically conductive material or an electrically conductivematerial can be deposited on the substrate such that the surface of thenanofluidic passage comprises such material.

A further exemplary method includes the steps of providing an array offluidic elements, each of the fluidic elements being connected to one ormore other fluidic elements in the array by one or more nanofluidicpassages, each of the nanofluidic passages including an electricallyconductive surface, and selectively closing one or more of thenanofluidic passages by causing an oxidized layer to electrochemicallygrow on the electrically conductive surface in selected nanofluidicpassages.

A further exemplary method includes the steps of forming a nanofluidicpassage having larger than targeted dimensions in a substrate, forming aconductive layer on the substrate, thereby reducing the dimensions ofthe nanofluidic passage, filling the nanofluidic passage with anelectrolyte, and electrochemically oxidizing the conductive layer untilthe fluidic passage has the targeted dimensions.

Another exemplary method includes providing a nanofluidic deviceincluding a nanofluidic passage having an electrically conductivesurface and an electrolyte within the nanofluidic passage and applying avoltage to the electrically conductive surface to electrochemicallychange the dimensions of the nanofluidic passage. The dimensions can beincreased or decreased.

An exemplary computer program product is provided for controlling thefabrication of a nanofluidic device including a nanofluidic passage in asubstrate, the nanofluidic passage comprising an electrically conductivesurface and containing an electrolyte. The product includes a computerreadable storage medium having computer readable program code embodiedtherewith, said computer readable program code comprising computerreadable program code configured to facilitate applying an electricpotential between the electrolyte and the electrically conductivesurface sufficient to cause oxidation of the electrically conductivesurface, and computer readable program code configured to monitor ioniccurrent through the nanofluidic passage.

As used herein, “facilitating” an action includes performing the action,making the action easier, helping to carry the action out, or causingthe action to be performed. Thus, by way of example and not limitation,instructions executing on a processor might facilitate an action carriedout by a remote device, such as a voltage supply, meter, microscopestage, or the like, by sending appropriate data or commands to cause oraid the action to be performed. For the avoidance of doubt, where anactor facilitates an action by other than performing the action, theaction is nevertheless performed by some entity or combination ofentities.

One or more embodiments of the invention or elements thereof can beimplemented in the form of a computer program product including atangible computer readable recordable storage medium with computerusable program code for performing the method steps indicated.Furthermore, one or more embodiments of the invention or elementsthereof can be implemented in the form of a system (or apparatus)including a memory, and at least one processor that is coupled to thememory and operative to perform exemplary method steps. Yet further, inanother aspect, one or more embodiments of the invention or elementsthereof can be implemented in the form of means for carrying out one ormore of the method steps described herein; the means can include (i)hardware module(s), (ii) software module(s), or (iii) a combination ofhardware and software modules; any of (i)-(iii) implement the specifictechniques set forth herein, and the software modules are stored in atangible computer-readable recordable storage medium (or multiple suchmedia).

Techniques of the present invention can provide substantial beneficialtechnical effects. For example, one or more embodiments may provide oneor more of the following advantages: 1) fabricating nanofluidic deviceswith feedback control; 2) allowing channel or pore sizes to be expandedor narrowed following fabrication; 3) facilitating the filling ofnanofluidic devices with aqueous solutions or other liquids.

These and other features and advantages of the present invention willbecome apparent from the following detailed description of illustrativeembodiments thereof, which is to be read in connection with theaccompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A-1D show a series of steps for fabricating a fluidic devicehaving one or more channels with selected dimensions;

FIGS. 2A-2D show a series of steps for fabricating a fluidic devicehaving one or more nanopores with selected dimensions;

FIG. 3 shows the ionic current through a fluidic passage prior to andduring electrochemical oxidation of a metal layer;

FIG. 4 shows a customizable fluidic device comprising a plurality offluidic elements;

FIG. 5 is a schematical illustration showing a software module forcontrolling the fabrication of nanofluidic devices;

FIG. 6 depicts a computer system that may be useful in implementing oneor more aspects and/or elements of the invention;

FIG. 7 is a schematic illustration of a test device for changing thediameter of a nanopore;

FIGS. 8A and 8B show a nanofilter membrane prior to and followingelectrochemical oxidation;

FIG. 9 is a schematical illustration of a fluidic device including ananofilter membrane, and

FIG. 10 shows a sequence of steps for fabricating a nanofilter.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

Fabrication of nanoscale fluidic elements may be difficult and canrequire non-standard and/or non-scalable techniques. The presentinvention allows devices to be created using scalable lithographic orother techniques followed by processing techniques that provide thedesired dimensions of the fluidic passages of the elements.

Devices including nanofluidic passages such nanopores and/ornanochannels are provided by the invention. As discussed below, thedevices may have properties that allow customization and versatility.Principles of the invention are further employed to provide a deviceincluding array of fluidic elements including one or more mechanisms tocontrol fluid flow. The fabrication of such devices can be facilitatedby employing methods of manufacture as disclosed herein.

FIGS. 1A-1D and 2A-2D show manufacturing steps for fabricating fluidicdevices having nanochannels and nanopores, respectively. Referring firstto FIG. 1A, a fluidic device 10 is formed through lithographictechniques to include a channel 12 running parallel to the surface ofthe device. Lithographic techniques typically employ the use of aphotoresist that is subjected to patterns of light while on a substrateand then removed in part to expose selected portions of the substrate.Subsequent etching steps and other processing result in features such asholes or channels being formed on the substrate. In the exemplary deviceshown in FIG. 1A, a layer 14 comprising silicon dioxide, silicon orother suitable material(s) is deposited on a substrate or base 16. Thislayer preferably has isotropic etch characteristics. The layer 14 may bedeposited by atomic layer deposition, chemical vapor deposition,physical vapor deposition, thermal oxidation or other suitableprocedure. The base 16 may be comprised, for example, of silicon,quartz, or silicon nitride, and is different in composition from thelayer 14 deposited thereon.

A layer 20 of silicon nitride, silicon dioxide or other suitablematerial that is not identical to the material(s) comprising layer 14,is deposited on layer 14 by procedures such as atomic layer deposition,chemical vapor deposition, or physical vapor deposition. A channelopening 18 is formed in the layer 20 using lithographic techniques suchas photolithography or electron beam lithograph. A channel 12 is formedin the layer 14 by etching the layer 14 through the channel opening 18,The substrate or base 16 of the device functions as an etch stop. Thechannel 12 has dimensions that are larger than the dimensions that areultimately desired, preferably no more than one hundred nanometers inany cross sectional direction. The layer 20 is laterally underetchedduring fabrication such that the width of the channel opening 18 issmaller than that of the channel 12, resulting in the device as shown inFIG. 1A. As discussed below, the undercut beneath the top layer 20facilitates closing the opening 18 above the channel 12.

The thickness of the base 16 may be between about 0.25 to 1.0 mm, but isnot considered critical. The thickness of the deposited layer 14 dependson the requirements of the device such as channel size. In thisexemplary embodiment, the thickness of this layer is between 10 and1,000 nm. The thickness of the top layer 20 is at least about 50 nm inthickness so that the undercut can be formed with mechanical stability.It is preferably no thicker than what is required to provide suchstability. The channel diameter is about one hundred nanometers or lessprior to subsequent processing.

Referring to FIG. 1B, the fluidic device 20 is coated by a conductor 22such as an electrochemically active metal. Such coating can be providedby techniques such as atomic layer deposition (ALD) or chemical vapordeposition (CVD). Metals such as titanium, tantalum, and tungsten areamong the materials that can be deposited. Metal alloys may also bedeposited. Selection of the materials may depend on the oxides that willbe formed as the device is further processed. It will be appreciatedthat, in certain circumstances, metal may be deposited prior to channelor pore formation and that features such as channels or pores can formedin or through the metal through lithographical/etching techniques. Inthe exemplary embodiment, the deposited conductor 22 forms a seal toclose off the opening 18 to the channel 12. The dimensions of thechannel are also reduced by an amount commensurate with the thickness ofthe deposited conductor that forms the surface of the nanochannel.

The coated fluidic device 10 is filled with an electrolyte 24 such aswater or an electrolyte solution as shown in FIG. 1C. Filling the deviceis facilitated by the fact that the channel 12 is larger than itsultimate target size (e.g. ten nm in diameter or less) even with theconductor coating. An electric potential may be applied to theelectrolyte across the fluidic passage to measure the ionic currentthrough the device. The current is proportional to the internaldimensions of the passage. Accordingly, the dimensions of the passagecan be determined at this time. The electrodes for creating the ioniccurrent are placed in or near each end of the fluidic passage (channel12 in the exemplary embodiment). The electrodes may, for example, beAg/AgCl, Au or Pt wire electrodes. The dimensions of the channel 12 arereduced in size by forming an oxide layer 26 on the conductor 22, asshown in FIG. 1D. This process is preferably feedback controlled bymeasuring the ionic current through the device as an electricalpotential is applied to the conductor 22. The voltage is applied to thedeposited conductor 22 using needle probes, alligator clips or wirebonding. Voltages may range be between 0.5 and 5.0V in typicalapplications.

FIG. 3 shows the current through the device as the oxidation layer growsfrom the starting point “A” corresponding to FIG. 1C to the end ortarget point “B” corresponding to FIG. 1D. The channel dimensions can bemonitored continuously or by repeatedly alternating electrochemicaloxidation and ionic current measurements. The process is discontinuedwhen the current reaches a level representative of the target channeldimensions, which can be a range of acceptable dimensions. If the oxidelayer 26 is insulating, the metal-oxide stack could then function as agate for altering the surface charge of the device 10 for use in furtherchemical functionalization, as a nanofluidic transistor, or as a sensordevice for chemicals or biological analytes in the fluid. Such a devicecould also be used as a DNA sensor and/or sequencer. Examples ofinsulating metal oxides include titanium oxides and platinum oxides. Itwill be appreciated that conducting oxides could alternatively be formedsuch as aluminum zinc oxide (AZO) or ruthenium oxide.

Methods according to the invention are applicable to the formation ofnanopores running orthogonal to the surface of the device as well aschannels 12 that extend parallel to the surface. Referring to FIG. 2A, adevice 30 includes layers 14, 16 and 20 similar to those found in FIGS.1A-1D. The device is fabricated in a similar manner as the fluidicdevice 10 discussed above using lithographical techniques and etching. Apore 38 formed in the top layer 20 is in fluid communication with areservoir 32. The pore 38 can be substantially larger than the targetsize pore, and may be as much as about 100 nm in diameter. Like thechannel 12 in the previous embodiment, the pore is accordingly in thesize range considered nanofluidic. A pore having a diameter between twoand fifty nanometers can be formed using a transmission electron beam. Apore ten nanometers or larger in diameter can be formed using electronbeam or photolithographic patterning. (It will be appreciated that thepore may not be perfectly round, in which case the largest diameter maybe about 100 nm or less.) A coating 40 of a conductor such as a metal orother appropriate electrochemically active, electrically conductivematerial is deposited on the device 30 as shown in FIG. 2B. (Such acoating may be unnecessary if the top layer 20 is comprised of anelectrochemically active, electrically conductive material.) The poresize, though reduced by the coating 40, is still larger than the targetsize. The device is then filled with an electrolyte 24 such as water oran electrolyte solution. The relatively large dimensions of the fluidicportions of the device 30 facilitate introduction of the solution. FIG.2C shows the fluid-filled device. An electrical potential is thenapplied to the coating 40 in order to form a conductive or an insulatingmetal-oxide film 42 as shown in FIG. 2D. The size of the pore ismonitored as oxidation occurs. The electrochemical oxidation isdiscontinued when the pore reaches the target size. It will beappreciated that the target size may be a specific diameter or within aspecified range. Unlike the method shown in FIGS. 1A-D where the channelopening 18 is sealed off by the metal, the pore 38 remains openfollowing both metal deposition and oxidation in order to function as ananofluidic passage.

The formation of nanofluidic passages such as nanopores and nanofluidicchannels using the methods described above can be accomplished on a chipby chip, completely customized basis. The methods can also be applied tohigh-throughput processing done wafer by wafer. The wafers can beseparated into individual chips following processing. Pore and/orchannel formation using photolithographic techniques facilitateproduction as opposed to more cumbersome procedures such as TEMdrilling. Because the dimensions of the initially formed channels andpores are neither critical nor particularly small, initial processing ofthe chips or wafers in forming pores and/or channels is facilitated. Asdiscussed above, fluidic devices having relatively large dimensions arealso filled with electrolyte or other fluid more easily.

A test device 60 as shown in FIG. 7 can be used to demonstrate thefeasibility of the methods disclosed herein. The device includes a fivenanometer thin film 62 of TiN in a stack comprising layers 64, 66 ofSiO₂ and Si₃N₄, respectively. The device includes a fluidic cell 68containing a KCl solution. The TiN layer includes a pore 70 less thanone hundred nanometers in diameter and preferably smaller. About fourvolts are applied to the TiN away from the fluid volume using a contactpad and needle probe. The measured ionic conductance decreasessignificantly after a few minutes, indicating the pore 60 has decreasedin size.

Devices can be provided to end users in finished or semi-finished formseither as chips or wafers. The end users can perform the oxidationprocess to provide passages of selected dimensions. The oxidationprocess can be reversed if necessary to enlarge passage dimensions.

In accordance with further aspects of the invention, a generic,multipurpose array 50 of fluidic channels or elements 52 may be providedas shown in FIG. 4. Each element is connected to another element by anindividually addressable, electrochemically reducible nanofluidicpassage 54. The array is preferably fabricated with all connectionsopen. At the point of use, one or more of the reducible nanofluidicpassages 54 could be closed in order to redirect fluid flow or removecertain elements 52 from the overall array. As shown in FIG. 4, theoriginal array 50 shown to the left of the figure has been modified inthe two alternative ways to produce arrays 50A, 50B having twoalternative flowpaths. Native or partially reduced nanofluidic passages54 appear in solid lines while closed passages 56 are shown in brokenlines. The passages 54 may be formed in the same manner as the channels12 discussed above. Each passage 54 includes an electrically conductive,preferably metal coating (not shown) having an oxide layer that definesthe dimensions of the passage. Selected passages are closed by applyingelectric potential between the electrolyte within the passages and themetal coatings, causing further growth of the oxide layer (not shown)until the passage is entirely closed. The elements 52 can be designedfor any particular purpose such as controlling or changing theproperties of the fluid or of an entity present within the fluid. Itwill be appreciated that the passages 54 of the array 50 may includeonly a metal coating, allowing the end user to partially close certainpassages and completely close others through varying degrees ofoxidation of the metal coatings. As discussed above, the oxidationprocess can be reversed to open a previously closed passage 54 ifdesired.

A further exemplary embodiment of the invention is shown in FIGS. 8A and8B, and relate to the fabrication of a nanofilter having a largeplurality of nanofluidic passages using principles of the invention. Thenanofilter is fabricated from an electrically conductive substrate 80.The substrate 80 includes a plurality of nanopores 82 that can be formedusing lithographic techniques and etching. Alternatively, the nanoporescan be formed employing a technique known as Directed Self-Assembly(DSA). This technique involves the following steps: (i) a substratesurface is chemically functionalized so that nanoparticles, for exampleblock-copolymers, adhere on it upon dispersing a fluid containing suchnanoparticles onto the substrate surface, (ii) the membrane is annealedevaporating away the fluid leaving the nanoparticles on the substratesurface, and (iii) the nanoparticles are then used either as a positiveor negative hard etch mask to further transfer the nanoparticle arraypattern down into the substrate thus forming a nanopore membrane in thesubstrate. Upon flood-dispersion onto the functionalized substratesurface, nanoparticles form self-aligned pattern arrays comprising aself-defined spacing between neighboring particles without the need toperform any additional alignment and/or patterning processes. Spacingthereby depends on the type and size of the nanoparticles, topography ofthe substrate surface, as well as the type of functionalization thereof.One can achieve grating patterns as well as dot (i.e. nanopore)patterns.

FIG. 10 illustrates steps that can be employed for fabricating ananofilter in accordance with the invention. A metal film 79 isdeposited on a substrate 93 having dielectric properties. The filtermembrane is created by removing the center portion of the substrate 93,thereby forming an insulator 94 that supports the membrane. A pattern ofnanopores 82 is formed in the membrane portion of the metal layer 79using techniques as described above, thereby providing a nanofiltersubstrate 80. As described further below, voltage is applied to reducethe pore size until a desired filter size is reached.

The pores formed in the substrate 80 of the exemplary embodiment are onehundred nanometers or less in diameter, and are preferably similar insize. In this embodiment, the substrate is comprised of anelectrochemically active, electrically conductive material. Thedeposition of a metal coating on the substrate accordingly is notrequired. As shown in FIG. 8A, both relatively large and small particles84, 86 having sizes “A” and “B” are capable of passing through thepores. The substrate is placed in an electrolyte. A baseline reading ofconductance or current through the substrate membrane is obtained.Voltage is applied to the substrate 80 to cause the formation of anoxide layer 88 on the surfaces bounding the nanopores 82 as shown inFIG. 8B. When the pore sizes have been reduced to the target diameters,as evidenced by changes in current density or other suitable parameter,the process is discontinued. Referring again to FIG. 8B, the pores 82have been reduced in diameter such that only the relatively smallparticles 86 having size “B” or less are able to pass therethrough. Theresulting nanofilter 90 can be provided to users in the form of a waferor chip or incorporated within a fluidic device. It will be appreciatedthat the voltage applied to the nanofilter 90 can be reversed, therebyincreasing the diameters of the nanopores 82. In use, a liquid can bepassed through the filter via electro-osmosis or other suitabletechnique in order to filter particles larger than the pore sizes.

FIG. 9 is a schematic illustration of a nanofluidic device including asystem that may be used to increase or decrease pore diameters in asubstrate 80 or nanofilter 90 and provide feedback relating to porediameter. In this exemplary embodiment, an electrically conductivesubstrate 80 is mounted between first and second insulators 92, 94. Theporous membrane portion of the substrate 80 is positioned within aliquid cell 98 that contains an electrolyte. O-rings 96 provide sealsisolating part of the substrate 80 from the liquid cell 98. Anelectrical connection is made to the substrate outside the liquid cellby a needle probe or wire bond. A first microammeter 100 is provided formonitoring the voltage applied to the substrate. A second microammeter100 is employed for measuring current through the substrate 80 ornanofilter 90. The second microammeter provides feedback relating topore diameter as the ionic current is proportional to the sizes of thenanopores 82 in the substrate. The oxidation or reduction process can beterminated upon obtaining a reading from the second microammeter thatcorresponds to a targeted average pore diameter. It will be appreciatedthat the measurement of the ionic current through the membrane portionof the substrate 80 can be expressed in units of conductance. Theconductance decreases as pore diameter decreases.

FIG. 5 provides a schematical illustration of a system for controllingthe fabrication methods discussed above. The system includes ananofluidic device 110 such as those discussed above, a software module112, and analog to digital/digital to analog converter 114. The softwaremodule includes a user interface 115 comprising a “set control voltages”control 116, a “set endpoint conditions” control 118, a “configure andset calculation algorithms” control 120, and a display 122 providing agraphical presentation of data and process state. The “set controlvoltages” control 116 allows the user to set the voltages employed forboth oxidizing the substrate (e.g. the metal substrate 80 or coatedfluidic devices 10 or 30) and causing an ionic current through thesubstrate. The “set endpoint conditions” control 118 provides theability to automatically terminate the oxidation (or reduction) processwhen the ionic current reaches a level corresponding to a targetednanopore or nanochannel size. The control 120 for configuring andsetting calculation algorithms allows the user to set the algorithmsemployed in a calculation module 124. The module memory stores adecision-making algorithm 126 that receives input from the “set endpointconditions” control 118. The decision making algorithm “controlalgorithms” software 126 and the “set control voltages” control 116provide input to “control algorithms” software 128.

The “control algorithms” software 128 controls the voltage applied forelectrochemical oxidation and/or reduction and process time. It furthercontrols the voltage for generating the ionic current through thenanofluidic device 110 when feedback relating to pore or channel size isrequired. Inputs relating to ionic current and surface current areprovided to the calculation module 124. The ionic conductance of thefluidic device is determined in the calculation module 124 which, inturn, provides conductance information to the decision-making algorithmsoftware 126. As the ionic conductance information is related to pore orchannel size, this information is provided to the decision-makingalgorithm 126 to determine whether further oxidation or reduction isrequired. Information from the calculation module 124 is also providedto the graphical display 122.

Given the discussion thus far, it will be appreciated that, in generalterms, an exemplary method, according to an aspect of the invention,includes the steps of providing a substrate comprising a nanofluidicpassage bounded by an electrical conductor, filling the nanofluidicpassage with an electrolyte, and causing the nanofluidic passage to atleast partially close by electrochemically forming an oxide layer on theconductor. The method is reversible so that the passage dimensions canbe increased. The substrate itself can comprise the electrical conductoror an electrically conductive film can be deposited on the substrate.

In accordance with a further aspect of the invention an exemplary methodincludes forming a nanofluidic passage having larger than targeteddimensions in a substrate, forming a conductive layer on the substrate,thereby reducing the dimensions of the nanofluidic passage, filling thenanofluidic passage with an electrolyte, and electrochemically oxidizingthe conductive layer until the fluidic passage has the targeteddimensions.

A further exemplary method comprises providing a nanofluidic deviceincluding a nanofluidic passage having an electrically conductivesurface and an electrolyte within the nanofluidic passage and applying avoltage to the electrically conductive surface to electrochemicallychange the dimensions of the nanofluidic passage. As discussed above,the nanofluidic passage can comprise passages such as nanopores ornanochannels. The method is also applicable to changing the dimensionsof a large plurality of passages at the same time such as passages foundin the membrane of a nanofilter.

A further exemplary method relates to use of an array of fluidicelements. Such a method comprises providing an array of fluidicelements, each of the fluidic elements being connected to one or moreother fluidic elements in the array by one or more nanofluidic passages.Each of the nanofluidic passages includes an electrically conductivesurface. The method further comprises selectively closing one or more ofthe nanofluidic passages by causing an oxidized layer toelectrochemically grow on the electrically conductive surface inselected nanofluidic passages. An array of fluidic elements connected bynanofluidic passages and a system for electrochemically changing orclosing the passages is further provided.

A computer program product is provided for controlling the fabricationof a nanofluidic device that includes a nanofluidic passage in asubstrate, the nanofluidic passage comprising an electrically conductivesurface and containing an electrolyte. A computer readable storagemedium having computer readable program code embodied therewithcomprises: computer readable program code configured to facilitateapplying an electric potential between the electrolyte and theelectrically conductive surface sufficient to cause oxidation of theelectrically conductive surface and computer readable program codeconfigured to monitor ionic current through the nanofluidic passage.

A nanofilter having a filter membrane including nanofluidic passagesthat can be electrochemically changed to larger or smaller sizes isfurther provided. As discussed above, the membrane can be comprised of aconductor or include a conductive coating that can be electrochemicallyoxidized. A nanofilter assembly provided as a further aspect of theinvention preferably includes a feedback mechanism for determining theionic current through the filter membrane as well as a mechanism forcausing electrochemical oxidation. The extent to which the nanofluidicpassages have been narrowed or expanded can be determined from thefeedback mechanism. FIG. 9 provides an exemplary embodiment of thenanofilter assembly including a filter membrane, a mechanism for causingoxidation, and a mechanism for determining ionic current. FIG. 8A showsthe membrane portion of a nanofilter that has been subjected tooxidation to reduce the size of the nanofluidic channels. The processcan be reversed to enlarge the nanofluidic channels.

Exemplary System and Article of Manufacture Details

As will be appreciated by one skilled in the art, aspects of the presentinvention may be embodied as a system, method or computer programproduct. Accordingly, aspects of the present invention may take the formof an entirely hardware embodiment, an entirely software embodiment(including firmware, resident software, micro-code, etc.) or anembodiment combining software and hardware aspects that may allgenerally be referred to herein as a “circuit,” “module” or “system.”Furthermore, aspects of the present invention may take the form of acomputer program product embodied in one or more computer readablemedium(s) having computer readable program code embodied thereon.

One or more embodiments of the invention, or elements thereof, can beimplemented in the form of an apparatus including a memory and at leastone processor that is coupled to the memory and operative to performexemplary method steps such as measuring ionic current and creating theelectric potential used for metal layer oxidation.

One or more embodiments can make use of software running on a generalpurpose computer or workstation. With reference to FIG. 6, such animplementation might employ, for example, a processor 602, a memory 604,and an input/output interface formed, for example, by a display 606 anda keyboard 608. The term “processor” as used herein is intended toinclude any processing device, such as, for example, one that includes aCPU (central processing unit) and/or other forms of processingcircuitry. Further, the term “processor” may refer to more than oneindividual processor. The term “memory” is intended to include memoryassociated with a processor or CPU, such as, for example, RAM (randomaccess memory), ROM (read only memory), a fixed memory device (forexample, hard drive), a removable memory device (for example, diskette),a flash memory and the like. In addition, the phrase “input/outputinterface” as used herein, is intended to include, for example, one ormore mechanisms for inputting data to the processing unit (for example,mouse), and one or more mechanisms for providing results associated withthe processing unit (for example, printer). The processor 602, memory604, and input/output interface such as display 606 and keyboard 608 canbe interconnected, for example, via bus 610 as part of a data processingunit 612. Suitable interconnections, for example via bus 610, can alsobe provided to a network interface 614, such as a network card, whichcan be provided to interface with a computer network, and to a mediainterface 616, such as a diskette or CD-ROM drive, which can be providedto interface with media 618. Interfaces can be provided to microammetersand/or current supplies and the like, over a network or other suitableinterface, analog-to-digital converter, or the like.

Accordingly, computer software including instructions or code forperforming the methodologies of the invention, as described herein withrespect to FIGS. 1A-D, 2A-D, 8A-B and 10 may be stored in one or more ofthe associated memory devices (for example, ROM, fixed or removablememory) and, when ready to be utilized, loaded in part or in whole (forexample, into RAM) and implemented by a CPU. Such software couldinclude, but is not limited to, firmware, resident software, microcode,and the like.

A data processing system suitable for storing and/or executing programcode will include at least one processor 602 coupled directly orindirectly to memory elements 604 through a system bus 610. The memoryelements can include local memory employed during actual implementationof the program code, bulk storage, and cache memories which providetemporary storage of at least some program code in order to reduce thenumber of times code must be retrieved from bulk storage duringimplementation.

Input/output or I/O devices (including but not limited to keyboards 608,displays 606, pointing devices, and the like) can be coupled to thesystem either directly (such as via bus 610) or through intervening I/Ocontrollers (omitted for clarity).

Network adapters such as network interface 614 may also be coupled tothe system to enable the data processing system to become coupled toother data processing systems or remote printers or storage devicesthrough intervening private or public networks. Modems, cable modem andEthernet cards are just a few of the currently available types ofnetwork adapters.

As used herein, including the claims, a “server” includes a physicaldata processing system (for example, system 612 as shown in FIG. 6)running a server program. It will be understood that such a physicalserver may or may not include a display and keyboard.

As noted, aspects of the present invention may take the form of acomputer program product embodied in one or more computer readablemedium(s) having computer readable program code embodied thereon. Anycombination of one or more computer readable medium(s) may be utilized.The computer readable medium may be a computer readable signal medium ora computer readable storage medium. A computer readable storage mediummay be, for example, but not limited to, an electronic, magnetic,optical, electromagnetic, infrared, or semiconductor system, apparatus,or device, or any suitable combination of the foregoing. Media block 618is a non-limiting example. More specific examples (a non-exhaustivelist) of the computer readable storage medium would include thefollowing: an electrical connection having one or more wires, a portablecomputer diskette, a hard disk, a random access memory (RAM), aread-only memory (ROM), an erasable programmable read-only memory (EPROMor Flash memory), an optical fiber, a portable compact disc read-onlymemory (CD-ROM), an optical storage device, a magnetic storage device,or any suitable combination of the foregoing. In the context of thisdocument, a computer readable storage medium may be any tangible mediumthat can contain, or store a program for use by or in connection with aninstruction execution system, apparatus, or device.

A computer readable signal medium may include a propagated data signalwith computer readable program code embodied therein, for example, inbaseband or as part of a carrier wave. Such a propagated signal may takeany of a variety of forms, including, but not limited to,electro-magnetic, optical, or any suitable combination thereof. Acomputer readable signal medium may be any computer readable medium thatis not a computer readable storage medium and that can communicate,propagate, or transport a program for use by or in connection with aninstruction execution system, apparatus, or device.

Program code embodied on a computer readable medium may be transmittedusing any appropriate medium, including but not limited to wireless,wireline, optical fiber cable, RF, etc., or any suitable combination ofthe foregoing.

Computer program code for carrying out operations for aspects of thepresent invention may be written in any combination of one or moreprogramming languages, including an object oriented programming languagesuch as Java, Smalltalk, C++ or the like and conventional proceduralprogramming languages, such as the “C” programming language, BASICprogramming language, or similar programming languages. The program codemay execute entirely on the user's computer, partly on the user'scomputer, as a stand-alone software package, partly on the user'scomputer and partly on a remote computer or entirely on the remotecomputer or server. In the latter scenario, the remote computer may beconnected to the user's computer through any type of network, includinga local area network (LAN) or a wide area network (WAN), or theconnection may be made to an external computer (for example, through theInternet using an Internet Service Provider).

Aspects of the present invention are described herein with reference toflowchart illustrations and/or block diagrams of methods, apparatus(systems) and computer program products according to embodiments of theinvention. It will be understood that each block of the flowchartillustration and/or block diagram, such as provided in FIG. 5, andcombinations of blocks in the flowchart illustration and/or blockdiagram, can be implemented by computer program instructions. Thesecomputer program instructions may be provided to a processor of ageneral purpose computer, special purpose computer, or otherprogrammable data processing apparatus to produce a machine, such thatthe instructions, which execute via the processor of the computer orother programmable data processing apparatus, create means forimplementing the functions/acts specified in the flowchart and/or blockdiagram block or blocks.

These computer program instructions may also be stored in a computerreadable medium that can direct a computer, other programmable dataprocessing apparatus, or other devices to function in a particularmanner, such that the instructions stored in the computer readablemedium produce an article of manufacture including instructions whichimplement the function/act specified in the flowchart and/or blockdiagram block or blocks.

The computer program instructions may also be loaded onto a computer,other programmable data processing apparatus, or other devices to causea series of operational steps to be performed on the computer, otherprogrammable apparatus or other devices to produce a computerimplemented process such that the instructions which execute on thecomputer or other programmable apparatus provide processes forimplementing the functions/acts specified in the flowchart and/or blockdiagram block or blocks.

The flowchart and block diagram in the Figures illustrate thearchitecture, functionality, and operation of possible implementationsof systems, methods and computer program products according to variousembodiments of the present invention. In this regard, each block in theflowchart or block diagrams may represent a module, segment, or portionof code, which comprises one or more executable instructions forimplementing the specified logical function(s). It should also be notedthat, in some alternative implementations, the functions noted in theblock may occur out of the order noted in the figures. For example, twoblocks shown in succession may, in fact, be executed substantiallyconcurrently, or the blocks may sometimes be executed in the reverseorder, depending upon the functionality involved. It will also be notedthat each block of the block diagrams and/or flowchart illustration, andcombinations of blocks in the block diagrams and/or flowchartillustration, can be implemented by special purpose hardware-basedsystems that perform the specified functions or acts, or combinations ofspecial purpose hardware and computer instructions.

It should be noted that any of the methods described herein can includean additional step of providing a system comprising distinct softwaremodules embodied on a computer readable storage medium; the modules caninclude, for example, any or all of the elements depicted in the blockdiagram and/or described herein; by way of example and not limitation,an initialization module, a module to cycle through the test points andparameters, an output module to generate the output file, apost-processing module to reduce the data and search for anomalies, andthe like. The method steps can then be carried out using the distinctsoftware modules and/or sub-modules of the system, as described above,executing on one or more hardware processors 602. Further, a computerprogram product can include a computer-readable storage medium with codeadapted to be implemented to carry out one or more method stepsdescribed herein, including the provision of the system with thedistinct software modules

In any case, it should be understood that the components illustratedherein may be implemented in various forms of hardware, software, orcombinations thereof; for example, application specific integratedcircuit(s) (ASICS), functional circuitry, one or more appropriatelyprogrammed general purpose digital computers with associated memory, andthe like. Given the teachings of the invention provided herein, one ofordinary skill in the related art will be able to contemplate otherimplementations of the components of the invention.

The terminology used herein is for the purpose of describing particularembodiments only and is not intended to be limiting of the invention. Asused herein, the singular forms “a”, “an” and “the” are intended toinclude the plural forms as well, unless the context clearly indicatesotherwise. It will be further understood that the terms “comprises”and/or “comprising,” when used in this specification, specify thepresence of stated features, integers, steps, operations, elements,and/or components, but do not preclude the presence or addition of oneor more other features, integers, steps, operations, elements,components, and/or groups thereof.

The corresponding structures, materials, acts, and equivalents of allmeans or step plus function elements in the claims below are intended toinclude any structure, material, or act for performing the function incombination with other claimed elements as specifically claimed. Thedescription of the present invention has been presented for purposes ofillustration and description, but is not intended to be exhaustive orlimited to the invention in the form disclosed. Many modifications andvariations will be apparent to those of ordinary skill in the artwithout departing from the scope and spirit of the invention. Theembodiment was chosen and described in order to best explain theprinciples of the invention and the practical application, and to enableothers of ordinary skill in the art to understand the invention forvarious embodiments with various modifications as are suited to theparticular use contemplated.

What is claimed is:
 1. A method of fabricating a nanofluidic device,comprising: forming a nanofluidic passage having larger than targeteddimensions in a substrate, wherein the nanofluidic passage is a channelformed with an opening in a surface of the substrate; forming aconductive layer on the substrate, thereby reducing the dimensions ofthe nanofluidic passage and closing the opening; filling the nanofluidicpassage with an electrolyte; electrochemically oxidizing the conductivelayer until the fluidic passage has the targeted dimensions; monitoringthe size of the nanofluidic passage by measuring ionic current throughthe nanofluidic channel; and discontinuing electrochemically oxidizingthe conductive layer when the ionic current reaches a levelcorresponding to the targeted dimensions.
 2. A method of fabricating ananofluidic device, comprising: obtaining a structure including a baseand a non-metallic layer on the base; forming a nanochannel within thenon-metallic layer of the structure; forming an electrically conductivelayer within the nanochannel, the electrically conductive layer forminga surface of the nanochannel having a bottom portion extending over thebase and sidewall portions adjoining the non-metallic layer;electrochemically oxidizing the electrically conductive layer to reducethe dimensions of the nanochannel by: filling the nanochannel with anelectrolyte; and applying a voltage to the electrically conductivelayer, thereby forming an oxide layer on the electrically conductivelayer, the oxide layer adjoining the bottom portion and the sidewallportions of the electrically conductive layer; creating an ionic currentthrough the nanochannel; measuring the ionic current; monitoring thesize of the nanofluidic passage by measuring ionic current through thenanochannel; and discontinuing electrochemically oxidizing theelectrically conductive layer when the ionic current reaches a levelcorresponding to targeted dimensions of the nanochannel.
 3. The methodof claim 2, wherein the structure further includes a top layer on thenon-metallic layer, further including: forming a channel opening withinthe top layer of the structure; and closing the channel opening whileforming the electrically conductive layer.
 4. The method of claim 2,further including reversing the voltage applied to the electricallyconductive layer, thereby enlarging the dimensions of the nanochannel.5. The method of claim 2, wherein the nanochannel extends down to thebase, the bottom portion of the electrically conductive layer beingformed within the nanochannel and on the base.